The objective is to evaluate changes in the temporal evolution and regional distribution of the arterial brain Doppler parameters in relation to different stages of hemodynamic adaptation in severe intrauterine growth restriction (IUGR).

IUGR associated with placental insufficiency and chronic hypoxia may complicate nearly 3-4% of all pregnancies. Up to 15% of all IUGR fetuses develop some degree of overt neurological damage, mainly expressed as hypoxic-ischemic encephalopathy, leukomalacia, and/or cerebral palsy. However, as more data becomes available, a wider spectrum of subtle brain developmental disturbances has been described, including neuromuscular disorders, learning disabilities and behavioural misconducts. The understanding of the adaptive processes occurring in the human fetal brain under growth restriction, and subsequently, the ability to predict neurological morbidity is still poor. In spite of the use of Doppler in the obstetrical management, the risk of suboptimal neurodevelopment in childhood in fetuses diagnosed with IUGR may occur in up to 50-60% of cases.

Growth restriction due to placental insufficiency is believed to be associated with chronic hypoxia, which in turn, triggers a blood flow centralisation process in order to maximise blood supply to key organs, such as the brain heart and adrenals. The temporal evolution of these changes during the process of fetal deterioration within the fetal brain, and the potential existence of regional variations has not been explored. In clinical practice, the centralisation process is identified by a reduction in the pulsatility index (PI) in the middle cerebral artery (MCA). It is unknown if these changes occur similarly in all cerebral arteries and their relationship to the fetal hemodynamic adaptation to severe growth restriction.

There are few reports addressing the simultaneous investigation of the main fetal cerebral arteries. In normal pregnancies, Hata et al. reported a reduction in the resistance index of the ACA, MCA and PCA from 28 weeks onwards. In IUGR fetuses, van den Wijngaard et al. showed a constantly reduced PCA-PI value (mean <2SD) as compared with MCA-PI and ACAPI. Conversely, Noordam et al. found that MCA-PI was the artery with the most pronounced changes in IUGR fetuses and, recently Dubiel et al. in a group of high-risk pregnancies, described that ACA-PI showed the highest association with an adverse perinatal outcome. All these studies agree with the notion of a general reduction in the cerebral vascular resistance, but differ on which vessel is most affected. A poor case-specific definition of IUGR, lack of longitudinal evaluation, and differences in severity and gestational age at enrolment could explain the reported differences. Our findings are in line with those by Dubiel et al., who described the ACA as the artery showing the earliest changes in growth restriction. In addition, in this study we also found that the PCA also presented an earlier response. This observation is based on, despite in hemodynamic stage 1 all fetuses have a normal MCA-PI value, some of them already showed significantly reduced ACA-PI and PCA-PI values, as compared with controls.

Another observation in this study was that from stage 2 onwards, PI values failed to decrease. It is possible that the fetal brain reaches the maximal vascular vasodilation response already by stage 2, as defined in this study. In the presence of more severe hemodynamic changes (reverse umbilical end diastolic flow and absent or reverse atrial flow in the ductus venosus) PI values from the MCA and PER arteries even tended to increase. This finding was previously reported by Konje et al. who described an increment in MCA-PI, or reversal adaptation, in severely affected IUGR fetuses. They also described a reduction in the MCA volume blood flow prior to the increment in the MCA-PI. The opposite pattern observed between MCATAMV and MCA-PI at hemodynamic stages 3 and 4 are in accordance with this observation. Furthermore, we observed a similar behaviour in the pericallosal artery.